Folding Proteins

I recently heard a podcast about folding proteins.  It was an interview of a company that thinks their scientists have figured out a therapy to refold misfolded proteins in an animal's body.  Protein folding is a complex subject I won't try to pretend that I understand well.  What I do understand is fascinating.  I've been studying starch lately, and I know that when you heat starch up to a high enough temperature, it denatures, which means that the way it is folded becomes unraveled.  This is why your jello pudding goes from liquid to a gel.  DNA does this complex dance when cells divide, where it unwraps itself and rewraps itself back into a double helix that is wound around itself in a complex pattern.  I liken the close up view of a strand folding to the way a stream sometimes meanders in a valley, looping back on itself.

There are two other instances of protein folding that I know about.  One is prion based diseases like Mad Cow Disease and its human form, Creutzfeldt–Jakob's disease (also known as Chronic Wasting Disease in deer).  I once heard that the prion acts a little bit like a virus, except that it's not even RNA, it's just a protein, but its misfolded shape spreads once it's in a new host, and the misfolded proteins damage the functionality of the brain.  I don't think that is an accurate scientific description, and I'm not certain that the disease is even understood in that much detail at this time, but that's an approximation of some descriptions I've heard in the past, and I was impressed with the knowledge that the good protein and the bad protein are the same combinations of atoms in the same order, in effect the same molecular description, but just folded into a different shape, and therefore not chemically equal.  I find this to be fascinating.  It makes biology seem like a miracle when you consider that everything must work perfectly in order to work at all.  I guess it's not that surprising that shape matters, if you consider anything else you were going to make, just throwing the ingredients together in a pile means nothing, they have to be assembled into the right structure.  You couldn't just throw bricks and mortar together hap hazardously and expect to make a house.

The other protein folding disease I have heard about is Alzheimer's Disease.  Again, this may not be the correct understanding of the situation as it is now understood, and the scientific community will no doubt understand the biochemistry and mechanics of this disease much better some day than is understood right now.  From what I understand, there are amyloid plaques present in Alzheimer's victims that were thought to be related to misfolding proteins (I may be confusing this with tau protein tangles - I'm not researching this column, just writing it from memory).  One theory is that once the misfolded form is present in the brain that it spreads and disrupts the healthy function of the brain.

The company I started to explain about above is saying that they have come up with a way to refold proteins.  They claim that the body makes misfolded proteins all the time, and in most cases, the body recognizes the error and holds the proteins aside until it can break them back down into their building blocks and recycle them or dispose of them.  If they can perfect and target this therapy, there are many other diseases and conditions that could be treated.  It's really cool technology.

But the trivial reason I sat down to write this post is a bit different that folded proteins.

I was recently travelling, and one of the people at our meeting during the day begged off going to dinner because he said that he thought that his diverticulitis was acting up.  My understanding is that this means that there is a pocket in the intestines that forms a little closed off sack and gets something irritating in it, which then causes the intestinal wall to swell and further trap a portion of material.  This can cause breakdown of the intestine wall and subject that closed off portion to an infection.  This is why you should eat a diet high in fiber, kids.  Gotta keep things moving along and scoured out clean.

Anyway, I got very sick after going to dinner that night.  This started a gastrointestinal ordeal that lasted 5 days.  Did I eat something bad?  Did I have a shellfish allergy that I did not know about?  Did I catch some bug that was going around?  The guy I talked with that day was sick, maybe not with a chronic condition, but with something infectious.  Then I did something truly stupid on the way home.  While at the airport, I got a bag of Skittles.  I suspect that candies that have chemical thickeners in them could create partial blockages, creating a painful situation similar to Diverticulitis.  I had previously vowed to stay away from such foods, but unfortunately, had forgotten my vow and had not maintained healthy habits right at a time when I was already in distress.  So while feeling absolutely terrible for a few days, I spent a lot of time wondering if I needed to go see a doctor or if this was something that would resolve with a little time.  I read a lot of reports on the Mayo Clinic's site and wondered if it was possible that I had ingested some Salmonella (how could that be, and yet I was still somewhat functional - doesn't that stuff kill you?).  I wondered about the status or structure of my cilia lining my intestines.  You can really damage them, and within a few days, they will grow back.  I pondered celiac disease, and how that allergy can also damage cilia.

Then it all cleared up and I got better.  I was still thinking about it today, and I pondered the way the intestines loop around the abdominal cavity, packing such a long organ into such a tight space.  I was wondering how hard it is to have it get twisted or kinked and why it doesn't happen more often.  If you're out of shape with extra weight, it stands to reason that you're probably smashing or pinching your intestines, so why doesn't being morbidly obese tend to kill you?  How does being in shape help with the layout and routing of the intestine in the abdomen?  Does the routing change over time?  If you could trace out the path the way a kid traces a maze on a page, would it be different today that it was when you were little?  Would a group of 10 people each have different routing of their intestines, or would most people tend to have an identical route?

And then I put the two subjects together and wondered about how similar the folding of proteins is to the folding of intestines.  Is this a macro example of the same kind of phenomena?  How much do we really know about the shape of proteins' folds?  There is a website that crowdsources examination of protein folding possibilities, I've heard about it and done similar websites like Zooniverse, but I've never looked at it.

This just proves that you have a lot of time to think about shit when you're sick.